Recyclable photocatalyst perovskite as a single-electron redox mediator for visible-light-driven photocatalysis gram-scale synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones in air atmosphere

Based on the Biginelli reaction of β-ketoesters, arylaldehydes, and urea/thiourea, we created a green radical synthesis procedure for 3,4-dihydropyrimidin-2-(1H)-ones/thiones. A single-electron redox mediator was applied to a solution of ethanol in an air environment, at room temperature, and with blue LEDs as a renewable energy source in order to create. The objective of this research is to create a halide perovskite that is widely available, affordable, recyclable, and economically feasible. A factor mentioned in the discussion is that the procedure tolerates a variety of donating and withdrawing functional groups while still offering a very fast rate and excellent yields. The range of yields is quite uniform (86–94%, average: 90.4%), and the range of reaction times is very quick (4–8 min, average: 5.8 min). Furthermore, gram-scale cyclization shows that it is applicable for use in industry. Additionally, CsPbBr3 is quite stable and can be used six times in a row without experiencing significant structural changes or activity loss, which has been extremely helpful in meeting industrial needs and environmental issues.


Scientific Reports
| (2023) 13:10262 | https://doi.org/10.1038/s41598-023-37526-x www.nature.com/scientificreports/ A multitude of catalysts may be implemented in the synthetic production of 3,4-dihydropyrimidin-2-(1H)ones/thiones, including Cu/Cu 2 O@g-C 3 N 4 19 , N-(phenylsulfonyl)benzene sulfonamide 20 , h-BN/Fe 3 O 4 /Co 21 , Na 2 eosin Y 22 , copper(II)sulfamate 23 , bakers, yeast 24 , hydrotalcite 25 , hexaaquaaluminium (III) tetrafluoroborate 26 , TBAB 27 , copper (II) tetrafluoroborate 28 29 , triethylammonium acetate 30 , saccharin 31 , caffeine 32 , zirconium(IV)-salophen perfluorooctanesulfonate 33 , H 3 [PW 12 O 40 ] 34 , Dioxane-HCl 35 , 4CzIPN 36 , H 4 [W 12 SiO 40 ] 37 , Zr(H 2 PO 4 ) 2 38 , GO-chitosan 39 , and sodium dodecyl sulfate 40 . The prolonged reaction times, the exorbitant cost of reagents, tumultuous reaction mechanisms, and minimal product yields, foray into waste management concerns. Furthermore, the extraction of homogeneous catalysts from reaction mixtures poses a challenging task. In recent times, photocatalysts have been employed for the purpose of synthesizing heterocyclic chemicals [41][42][43] . It is noteworthy to highlight that the majority of widely used photocatalysts are essentially homogeneous in nature and consequently, they cannot be efficiently recovered in established techniques. Furthermore, the practical applications of these materials have been constrained by their high costs, elaborate synthetic preparations, requisite air-free reaction conditions, and often limited activity. This has led to their limited use in various fields. Consequently the advancement of heterogeneous photocatalysts that are facile to be fabricated and possess the attribute of facile catalytic separation and reusability is currently in high demand and thus holds significant importance. Over the past few years, there has been considerable interest in perovskites as a viable material for the efficient conversion of solar energy. This is attributed to several noteworthy advantages including their structural simplicity, exceptional optoelectronic properties, flexibility, and robust photo/thermal stability. It is noteworthy that these materials are frequently employed in a broad array of applications, including solar cells,  www.nature.com/scientificreports/ photodetectors, light-emitting diodes (LEDs), semiconductor lasers, and field-effect transistors. Nevertheless, the utilization of perovskites as photocatalysts in inducing organic bond formation remains relatively nascent, with much room for further exploration and development. In light of the optimum band gap of CsPbBr 3 for the absorption of visible light and the redox potential that grants the ability to function as a solitary-electron redox mediator, a variety of sophisticated organic reactions catalyzed by CsPbBr 3 have been documented. There remains a strong desire for additional analysis and investigation of innovative organic transformations facilitated by halide perovskites acting as photocatalysts, in order to produce high-value-added compounds via photosynthesis 44 . This discourse expresses our unwavering concern for the evolution of innovative sustainable synthetic techniques. In this regard, our current work expounds on our recent achievement; a visible-light-promoted procedure, which facilitated the successful undertaking of the Biginelli reaction of arylaldehydes in the presence of urea/thiourea and β-ketoesters employing reusable CsPbBr 3 as a heterogeneous photocatalyst. A noteworthy observation is a facile recovery and the ability to reutilize the photocatalyst for a minimum of six iterations while maintaining its aptitude for catalytic activities.
The current study utilizes a three-condensation domino reaction that exploits a single-electron transfer (SET) pathway. The system also takes advantage of blue light as a renewable energy source and air conditions, while operating at room temperature using ethanol as an environmentally benign solvent. The implementation of this particular approach offers a multitude of significant benefits, notably including superior step economy, expansive substrate scope, the ability to recycle the employed catalyst, and the utilization of eco-friendly solvents. Despite its successful completion devoid of any complications, punctually and within the financial parameters.

Experimental
General. The melting points of each chemical were determined utilizing a 9100 electrothermal instrument.
Furthermore, the 1 HNMR and 13 CNMR spectra were obtained utilizing DMSO-d 6 in conjunction with the Bruker DRX-300, DRX-400, and DRX-100 Avance instruments. Significant quantities of reagents were supplied by Fluka, Merck, and Acros, and expeditiously employed for the purposes intended.

A methodology for generating 3,4-dihydropyrimidin-2-(1H)-ones/thiones (4a-w).
In the presence of a 1 mol% loading of CsPbBr 3 , urea/thiourea (2, 1.5 mmol), ethyl/methyl acetoacetate (3, 1.0 mmol), and arylaldehyde derivatives (1, 1.0 mmol) were stirred at room temperature using 3 mL of EtOH as a solvent. The data was collected and documented via Thin-Layer Chromatography (TLC). Following the reaction, the resultant mixture underwent a thorough screening and washing protocol with EtOH. Subsequently, the crude solid was subject to crystallization using ethanol as a solvent, thereby obtaining the pure and pristine material without any supplementary purification measures. We aim to investigate the feasibility of synthesizing the aforementioned chemicals on a gram-scale within the context of pharmaceutical process research and development (R&D). In a single experimental procedure, 50 mmol of 4-methylbenzaldehyde, 75 mmol of urea, and 50 mmol of methyl acetoacetate were employed. Following a reaction duration of 4 min, the resultant product was acquired through the implementation of standard filtration methodology. Based on the 1 HNMR spectrum, it can be inferred that the chemical is spectroscopically pure. Through the analysis of the spectral characteristics of the products, specifically in terms of the 1 HNMR data, we have categorized them accordingly. The aforementioned Supporting Information document provides an extensive compilation of pertinent information.

Results and discussion
The present study aimed to investigate the interactions among benzaldehyde (1.0 mmol), urea (1.5 mmol), and ethyl acetoacetate (1.0 mmol) in EtOH solvent (3 mL). Upon incubation of 3 mL of EtOH without the presence of a photocatalyst for a duration of 30 min, an insignificant level of 4f was produced at ambient temperature, as illustrated in Table 1, entry 4. The incorporation of multiple supplementary photocatalysts expedited the chemical reaction. The aforementioned substances were observed to include CsPbBr 3 , PbBr 2 , CsBr, methylammonium lead tribromide (MAPbBr 3 ), methylammonium lead triiodide (MAPbI 3 ), and tricesium nonabromodibismuthate (III) (Cs 3 Bi 2 Br 9 ). Through the application of this technique, the synthesis of 4f can be accomplished with a varying yield between 32 and 94% as documented in Table 1. The aforementioned results facilitated the enhanced efficacy of CsPbBr 3 . According to the data presented in Table 1 in entry 2, the implementation of 1 mol% CsPbBr 3 led to a production yield of 93%. Table 2 at entry 10, shows that under solvent-free conditions, only 42% of product 4f is produced. Table 2 shows that the outcomes for toluene, CH 2 Cl 2 , DMSO, EtOAc, ethyl lactate, THF, MeOH, CH 3 CN, and DMF were noticeably lower; whereas the employment of EtOH as green solvent caused an increase in yield and facilitated the process. The reaction in ethanol demonstrated notable levels of both yield and reaction rate. Table 2, entry 1 provided the necessary data from which a yield of 93% was realized. Various light sources have been investigated in numerous studies to determine the impact of blue light on yield (as depicted in Table 2). The detection of 4f in the trace was facilitated by controlling the test in the absence of the light source. As per the findings of the research, the synthesis of product 4f necessitates the utilization of CsPbBr 3 in conjunction with visible light. The optimal parameters were determined via the utilization of blue LED power intensities amounting to 3 W, 7 W, and 10 W. Based on the findings presented in Table 2, entry 1, it can be concluded that the utilization of blue LEDs (7 W) resulted in optimal outcomes. Tests were performed on several substrates, as presented in Table 3 and Fig. 2, under optimal conditions. The resultant effect of the reaction remained unaltered by the presence of the benzaldehyde substituent, as indicated in Table 3. Within the scope of this reaction, substitutions involving polar and halide species were demonstrated to be permissible. The present state of the reaction permits both reactions involving electron-donating functional groups and those involving electron-withdrawing functional groups. The potential yield of aromatic aldehydes substituted in ortho, meta,  www.nature.com/scientificreports/ or para positions is considerably high. Ethyl acetoacetate and methyl acetoacetate exhibit analogous reaction characteristics. The reactiveness of urea and thiourea exhibited comparability. Table 4 furnishes data pertaining to the turnover frequency (TOF) and turnover number (TON). The concept of yield is classified into two types, namely TON (Turnover Number) and TOF (Turnover Frequency), which can be expressed as TON = Yield/Amount of catalyst (mol), TOF (min -1 ) = Yield/Time/Amount of catalyst (mol), respectively. Increased values of TON and TOF lead to enhanced catalyst efficiency by diminishing the amount of catalyst necessary for augmenting yields. The transistor 4f exhibits a high TON and TOF: 93 and 18.6, respectively. Similarly, the transistor 4u also displays a high TON: 92 and TOF: 18.4. The study's aims of optimizing yield, reducing reaction time, and minimizing recyclable photocatalyst usage are the focal points.
In order to assess the significance of air atmosphere, additional controlled experiments were conducted (Fig. 3). Upon purging the reaction with nitrogen gas (N 2 ), a yield of 43% for the formation of product 4f was observed. Nonetheless, the response carried out under stringent anaerobic circumstances using the Freeze-Pump-Thaw approach exclusively yielded 4f in a negligible amount. The reaction was executed under a nitrogen atmosphere that had undergone degassing through the utilization of the freeze-pump-thaw method. It was observed that the reaction came to a complete halt, which implied that oxygen (O 2 ) played an indispensable role. Nevertheless, in the absence of oxygen (O 2 ) during the reaction, it can be postulated that the reaction pathway involving oxygen is seemingly fundamental given the markedly low yield recorded in the oxygen-free control experiment.
Furthermore, Fig. 4 displays the findings of control examinations conducted to reveal the mechanism that underlies the three-component visible light-induced reaction. The Biginelli reaction is commonly believed to proceed via a two-step mechanism; the initial step involves the generation of benzylideneurea (I), whereas the terminal step involves the condensation of (I) with ethyl acetoacetate (3). The synthesis of benzylideneurea (I) was performed via the condensation reaction between benzaldehyde (1) and urea (2) under conventional conditions, utilizing CsPbBr 3 as a photocatalyst in ethanol solvent, facilitated by blue light emitting diode irradiation,  Reaction mechanism. Figure 5 delineates the proposed mechanism with comprehensive elaboration.
Upon exposure to visible light, the CsPbBr 3 underwent the creation of electrons in the conduction band (CB) and holes in the valence band (VB). As a result of being exposed to visible light, the absorption of a photon within CsPbBr 3 results in the creation of an electron and a hole, denoted as (e -) and (h + ), respectively. These entities are capable of functioning as singular electron donors and acceptors within a variety of desired organic transformations, according to the literature 45 .
The utilization of the single-electron transfer (SET) technique has facilitated the development of visiblelight-driven photocatalytic devices employing CsPbBr 3 , which exhibit the capability for recycling and serve as a promising candidate for halide perovskite-based applications. The acceleration of the process is facilitated by the presence of visible light. The present investigation concerns the SET activity of the CsPbBr 3 radical and arylaldehydes (1), which yields the regeneration of the ground-state CsPbBr 3  Recyclability of the catalyst. The recycling experiments were conducted to assess the durability and recyclability of CsPbBr 3 . The present study examines the potential for catalyst reusability in relation to CsPbBr 3 through the synthesis of 5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (4f). Upon the culmination of the reaction, the catalyst was removed through the application of centrifugal force, followed by filtration and washing with ethyl acetate (2 × 3 mL). Furthermore, the catalyst was dried using a vacuum without undergoing any additional purification steps prior to its successful reuse in subsequent reaction cycles. The graphical representation is depicted in Fig. 6. The catalyst exhibits a notable degree of reusability with up to six reuse cycles without significant reduction in activity level. This observation is suggestive of the remarkable activity and longevity of the catalyst under study. As an essential component of the work-up protocol, it was possible to salvage the CsPbBr 3 material and utilize it for the synthesis of 4f in up to six successive reactions with minimal loss of activity. The obtained results indicated a high level of operational efficiency, as demonstrated by the consistently favorable yield outcomes, namely: fresh (93%), run 1 (92%), run 2 (90%), run 3 (88%), run 4 (87%), run 5 (87%), and run 6 (85%). www.nature.com/scientificreports/ Table 5 presents a comparative analysis of the catalytic efficiency of multiple catalysts in the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones. This particular technique may be implemented in environments that are illuminated by visible light, recyclability of catalyst, involve modest quantities of photocatalyst, exhibit rapid reaction kinetics, and are characterized by the lack of any unintended by-products. Atom-economic methodologies exhibit remarkable efficacy and exert a significant influence on the industrial sector on a multigram scale.

Conclusion
In the radical Biginelli reaction, 3,4-dihydropyrimidin-2-(1H)-ones/thiones were produced by combining aldehydes, β-ketoesters, urea or thiourea. The novel recyclable halide perovskite; CsPbBr 3 was used to catalyze the reaction using the single-electron transfer (SET) technique of photosynthesis. At room temperature and in an airy setting, blue light can be used to generate a sustainable energy source in an ethanol solution. The method has a number of benefits, such as a quick reaction time, the absence of potentially toxic solvents, high yields, an efficient reaction process, stable conditions, and a renewable energy source. Without altering the outcome, a multigram scale reaction of model substrates can be expedited. Additionally, CsPbBr 3 was extremely stable and could be reusability for six times without experiencing any substantial structural changes or activity loss. The method can therefore be used in an environment that is both sustainable and profitable.